Nu&#39;-butyrylsulfanilamides



Patented June 2 7, 1950 Mar;tin E. Hultquist, Bound Brook, N. J., and

Elmore H. Northey, Stamfori-Qonn, .as s ignors, to American CyanamidCompany, New York,

N. Y., a corporation of Maine No Drawing. Original application December1 5 1944, Serial N0. 568,386.

Divided and this {application April 30, 1948, Serial No. 24,408

2 Claims.

This invention relates to N-butyrylsulfanilamide. The compound of thepresent invention and its salts may be represented by the formula:

in which X is hydrogen or a salt-forming metal.

The compound of the present invention belongs to the group ofN'-acylsulfanilamides of which N'-acetylsulfanilamide is known. Thecompound shows markedly greater activity against streptococcalinfections. When compared with the acetyl compound in a typical test inwhich the drug was administered as a suspension in oil and controlledanimals were used to assure the virulence of the bacteria, the controls,of course, dying, the N-butyrylsulfanilamide showed an average survivalof 80% of the mice inoculated with streptococci as against 47% for theacetyl compound. The activity against pneumococcal infections was onlyslightly less than the N'-acetylsulfanilamide.

The compound of the present invention may be prepared by two generalprocedures. One method is by reaction of butyryl chloride with theN-sodium salt of N acylsulfanilamide, such as N -acetylsulfanilamide,followed by hydrolysis of the N -acyl group. Another method is to reactsulfanilamide with butyryl chloride to produce the N -acylaminoN'-butyrylsulfanilamide, in such a case the acyl group being the same,namely the butyryl group, followed by hydrolysis. Inert solvents fromliquid bases such as tertiary amines, for example pyridine, may be used.

The invention will be described in greater detail in conjunction withthe following specific example. The parts are by weight.

EXAMPLE N-butyryl-N-acetylsulfanilamide Anhydrous N'-sodium N-acetylsulfanilamide was prepared as follows: crude N-acetylsulfanilamide paste as obtained in sulfanilamide manufacture wasdissolved by the addition of solid, powdered sodium hydroxide to form awarm solution of the N'-sodium-N -acetylsulfanilamide. This was treatedwith decolorizing carbon, then cooled and crystallized, when it formedlarge crystals containing much water of crystallization which werefiltered and washed with a little ice water. These crystals were meltedin a small amount of water and recrystallized to free from excesscaustic. As much of the adhering mother liquor was removed as possibleby filtration and the crystals were then dried in a vacuum oven at notover 50 C. until practically anhydrous, then at -70 C. until completelyanhydrous, as indicated by hydrolysis of a sample to sulfanilamide andtitration with nitrite. The resulting anhydrous material was finelyground and used for the following synthesis:

236 grams or 1 mole of the N'-sodium-N acetyl-sulfanilamide weresuspended in 400 cc. of anhydrous dioxane. 108 grams of butyryl chlorideor 1 mol was added under agitation and when the reaction moderated, heatwas applied to maintain a slow boiling for 3 hours under refluxcondenser. The product was practically insoluble in the dioxane and wasremoved by filtration. It was recrystallized twice. from 2 liters ofalcohol using decolorizing carbon. Melting point was 238.2-240 C. Assayby sodium hydroxide was 98.4%. Crystals were needle shaped.

N -Butylrylsulfanilamide NHz-OSOzNHC 0 01120 H2013;

Hydrolysis of the acetyl group was accomplished by boiling one mol ofthe Nbutyryl- N -acetylsulfanilamide with 2.5 parts of sodium hydroxide,and 750 cc. parts of water for 1 hours. The mixture was acidified toabout pH 9 with hydrochloric acid, treated with decolorizers, cooled anda crop of sulfanilamide filtered 01f. The filtrate was then acidified toabout pH 4 and the crude N'-butyrylsulfanilamide crystallized oncooling. The product was recrystallized from water using decolorizingcarbon. It was soluble about l /z% near the boil. Assay by sodiumhydroxide titration, 100.2%; assay by nitrite titration, 100.6%.Theoretical molecular weight was 242.3. Melting point was 1l6.1117.3 C.Crystals were in the form of lon prisms.

a 3 I In the examples, N -acetylsulfanilamide has 2.N'-butyrylsulfanilamide having the formubeen used in each case as thestarting material 1a: because it is cheap and readily available. Itshould be understood, however, that the invention is not limited to theuse of N -acetylsulf- 5 O anilamide and any other acyl derivative suchas formyl, propionyl, benzoyl, and the like, may MARTIN HULTQUIST besubstituted for the acetyl derivative. MORE 11 T EY,

This application is a division of our copending application, Serial No.568,386, filed December BEFEREN QESQCI TED 1944' now atent 2356,05?" Thefollowing references"are of record in the turn was copending with and acontmuatmn-mfile of this patent:

part of an earlier application of the same inventors, Serial No.259,382, filed March 2, 1939, UNITED STATES PATENTS which was abandonedon March 27, 1945. v 15 Number Name Date We claim: 7 2,411,495 DohrnNov. 19, 1946 1. N'-butyrylsulfanilamide having the formu oflaN-o-sogiolm in which X is a cation.

1. N''-BUTYRYLSULFANILAMIDE HAVING THE FORMULA: 